Pharmacokinetics

Question 1

6 rights of prescribing

Answer 1

Patient, drug, route, dose, time and outcome

Question 2

Pharmacokinetics [3]

Answer 2

• Facilitates safe and effective use of medicines
  
  • Determines optimal dosage regimen (dose, route, dose, interval, duration of treatment)
  • Predicts potential drug interactions

Question 3

Bioavailability

Answer 3

Fraction of drug that reaches systemic circulation

Question 4

First pass (pre-systemic) metabolism

Answer 4

• Refers to metabolism of drug prior to reaching systemic circulation
  
  • First pass effect -> Bioavailability

Question 5

Distribution

Answer 5

Process by which drug is transferred reversibly from the site of administration and is distributed throughout body tissues
From plasma, drugs have to cross the capillary membrane to enter interstitial space and cross the cell membrane to enter intracellular fluid

Question 6

Plasma binding protein

Answer 6

Many drugs bind to plasma proteins as they have low water solubility

Drugs bind non-specifically to albumin in plasma
Drug + protein Drug-Protein complex

Reversible and saturable
Unbound or free fraction distributes
Unbound protein responsible for clinical effect

Question 7

Highly bound protein drugs [6]

Answer 7

Warfarin 
Phenytoin 
Sulphonamides 
Ibuprofen 
Salicylates
Furosemide 
Competition or displaces predisposes patient to toxicity

Question 8

Factors affecting distribution [4]

Answer 8

• Lipid and water solubility
  
  • Drug particulate size
  • Drug protein binding
  • Environment - blood flow and pH

Question 9

Apparent volume of distribution [3]

Answer 9

• Concept to predict how extensively a drug is distributed throughout the body
  
  • Volume in which a drug appears to be distributed with concentration equal to that of plasma
  • Vd = Dose (mg) / Concentration (mg/L)

Question 10

Vd scores

Answer 10

Vd < 10L (warfarin)
• Highly protein bound drug so retained in plasma

Vd10-30L (gentamicin)
• Water soluble and low lipid solubility
• Distribute into interstitial fluid BUT not cell
• Dose on ideal body weight - avoid toxicity

Vd > 100L (amiodarone)
• Fat soluble and distribute into cell

Question 11

Prodrug [3]

Answer 11

Compound that is metabolised into pharmacologically active drug
Enalapril to enalaprilat
Codeine into morphine
Levodopa to dopamine

Question 12

Drug clearance [2]

Answer 12

• The sum of all the drug-eliminating processes, principally determined by hepatic metabolism and renal excretion.

•	It can also be defined as the theoretical volume of fluid from which a drug is completely removed in a given period of time.

Question 13

Low clearance causes [7]

Answer 13

• Normal variation
  
  • Renal impairment
  • Liver impairment
  • Enzyme inhibition
  • Genetic poor metaboliser
  • Neonate
  • Old age

Question 14

High clearance causes [4]

Answer 14

• Normal variation
  
  • Increased renal blood flow
  • Genetic hypermetabolism
  • Enzyme induction

Question 15

Half life provides information on

[3]

Answer 15

• Time course of drug elimination
  
  • Time course of drug accumulation
  • Choice of dose interval

Question 16

Cytochrome P450 inhibitors

Answer 16

Amiodarone
Ciprofloxacin
Erythromycin/Clarithromycin
Metronidazole
Fluconazole
Isoniazid
Alcohol (acute)
Grapefruit juice

Question 17

Cytochrome P450 inducers

Answer 17

Carbamazepine
Phenytoin
Rifampicin
Alcohol (Chronic)

Question 18

Cytochrome p450 drugs with narrow therapeutic index

Answer 18

•	Drug metabolised 
	•	by CYP450 with
	•	narrow therapeutic 
	•	index/window
	•	Eg. warfarin, aminophylline
\+ inhibitor